Acute Gastroenteritis

Dr.Sathyamoorthy M

Acute gastroenteritis
AGE Pathophysiology, Clinical assessment and Investigations Assessment and management of dehydration Other aspects of managing a child with AGE Follow-up and prevention Complications Dysentery Persistent diarrhoea AGE with hypernatraemic dehydration

AGE - Definition
Acute disease of the GIT due to infective cause leading to diarrhoea +/- vomiting of rapid onset +/- other symptoms including:
Nausea, anorexia Fever Abdominal pain

Diarrhoea = passage of excessively liquid or frequent stools with increased water content.
>3 loose stools /day Wide variation in patterns of stool. Diarrhoea a change from the norm

Epidemiology
Worldwide: 3-5 billion cases of AGE in children <5 years 1.5 million deaths annually (WHO 2004) ORT developed in late 1960s Deaths from diarrhoea in children <5 years
1979: 2002: 4.5 million 1.6 million

WHO: Bulletin of World Health Organization

Causes
Viruses (about 70%) Rotaviruses Noroviruses (Norwalk-like viruses) Enteric adenoviruses Caliciviruses Astroviruses Enteroviruses Protozoa (<10%) Giardia lamblia Entamoeba histolytica Cryptosporidium
Bacteria (10-20%) Shiga toxin producing E. coli Vibrio cholerae Non-typhoid Salmonella spp Salmonella typhi and S paratyphi Shigella spp Enteropathogenic E. coli Enteroinvasive E. coli Campylobacter jejuni Yersinia enterocolitica Clostridium difficile Helminths Strongyloides stercoralis

Case 1
8 month old infant Loose stools Vomiting

Case 1- History
Age
For DD (eg. 6 mths intussusception, lower the age, higher the risk, st in infants < 12mths

Onset and duration:

duration risk of dehydration and complications Constipation followed by diarrhoea Salmonella Protracted diarrhoea secondary lactose intolerance, bacterial or protozoan infections

Diarrhoea
Watery Viral, profuse watery cholera, enterotoxic E. coli Blood and mucus Shigella, shigatoxin producing E. coli, Campylobacter and enteroinvasive E. coli Frequency and amount for assessment of dehydration and risk (>8/day - risk)

Case 1- History
Vomiting
Frequency and amount - risk of dehyration (>2/day - risk), need for iv fluid, DD meningitis, systemic infections Blood stained vomitus DHF, Mallory Weiss Bilious vomiting, projectile vom. surgical / int. obstruction

Fever
High fever shigellosis, enteroinvasive E.coli, campylobacter, other infections (UTI) High swinging fever - Salmonella typhi/paratyphi Persistent high fever septicaemia, DF, other infections

Abdominal pain
Salmonella, Shigella, enteroinvasive bacteria, (+tenesmus) DD Sx: intususception in infants, ac. Appendicitis, UTI

Case 1- History
Thirst for assessment of dehydration UOP (should be >1ml/kg/hr)
Frequency Last passage of urine

LOC
for assessment of dehydration DD meningitis, encephalitis in Salmonella spp.

Systemic inquiry for other infections, and other problems H/o antibiotic use
AB induced diarrhoea, Clostridium difficile

Case 1- History
Feeding history
Bottle-feeding and bottle washing / sterilizing

Contact history of diarrhoea in family / household

Viral AGE more likely with good hygiene practices

Hygiene practices
Handwashing, boiling of drinking water

DD AGE and complications

Infective AGE Commonest Acute watery diarrhoea (viral)
>3 stools/day No blood in stools

Cholera
Diarrhoea with severe dehydration during cholera outbreak Stool culture +ve for Vibrio cholera O1 or O139

Dysentery blood in the stool Persistent diarrhoea lasting > 14 days Diarrhoea with severe malnutrition Diarrhoea with AB use

DD less common
Other DD: Other infections
Systemic: septicaemia, meningitis, DF Local: UTI, URTI, hepatitis A

Surgical: intestinal obstruction

vomiting, abd pain / crying attacks > diarrhoea pyloric stenosis, intussusception, acute appendicitis, necrotizing enterocolitis, Hirschprung disease

Metabolic
Diabetes mellitus/DKA and Inborn errors of metabolism

Other
coeliac dis, cows milk protein intolerance, adrenal insuf., Reyes synd

Chronic constipation with overflow incont. spurious diarrhoea

Pathophysiology
Protective mechanisms of GIT
acid content of the stomach IgA secreted by the small intestine IgA in breast milk

Limit growth of bac in upper small intestine predominance of lactobacillus and bifidobacteria in lower GIT

Pathophysiology - Viral
Rotavirus attacks mature enterocytes at the tips of the small intestinal villi killed and shed into lumen of immature crypt-like cells + shortening of villi (pic) absorptive and disaccharidase activity + Ca mediated active secretion of fluids and electrolytes DIARRHOEA

Pathophysiology - Bacterial
Enterotoxic E. coli and Vibrio enterotoxins
promote Cl- mediated active secretion of fluids + electrolytes profuse watery diarrhoea Na linked co-transport preserved severe mucosal damage May take many weeks to recover

Enteropathogenic E. coli adhere to the brush border membrane of SI

Shigella species and E. coli serotypes O124 and O164 invade colonic mucosa (enteroinvasive)
Watery / mucoid diarrhoea and dysentery Blood and pus in stool Pain and tenesmus High fever ( febrile convulsions)

Clostridium difficile prod. cytotoxins direct toxic effect on enterocytes

Complications
Dehydration Metabolic disturbances:
Hypernatraemic dehydration
lethargy and irritability (particularly marked in hypernatremic dehydration) rapid correction with i.v. fluids fluid shifts across BBB cerebral edema convulsions or even death

Hyponatraemia Loss of HCO3- and K+ in stool, poor tissue perfusion, Metabolic acidosis hypokalaemia may have severe metabolic derangement hypoglycemia ketosis renal failure

Complications
Carbohydrate (lactose, glucose) intolerance milk intolerance Bloody diarrhea (in Shigella, Salmonella, Campylobacter and E. coli O157) HUS (E. coli O157) Iatrogenic complications from inappropriate iv fluid Susceptibility to re-infection Death

Case 1
8 month old baby 2 day h/o:
Mod. fever, intermittent Loose watery greenish stools x10 /d, mucus +, no blood, mod. large amount Vomiting 3 times 1 day, no htemesis, nonbilious, food and fluids given, mod. amount UOP fair, passed w stools Mother is worried because baby is irritable and not taking anything orally

Case 1
Examination:
*Weight recent weight loss deg. of dehydration Temperature LOC and general condition Assess hydration Abdomen: distension / mass / tenderness Nutritional status malnutrition Systemic examination for other infections Inspect stools for blood

Assessment
Risk of dehydration age
(highest in infants<12m)

frequency of watery stools

(>8/day)

Degree of dehydration *recent weight loss thirst oliguria Clinical examination:

*altered LOC *prolonged skin-pinch, *dry oral mucosa, *sunken eyes tears sunken fontanelle CRT

vomiting (>2/day) Nutrition

(malnutrition increases risk of complications, esp. electrolyte disturb.) Pathogen (Vibrio cholerae)

Sensitivity & specificity, <2sec - v. unlikely in severe dehydration

Haemodynamic status tachycardia, peripheral pulses, BP, cold peripheries (vasoconstriction) tachypnoea *signs of proved value [I,A] signs of severe dehydration

Assessment of Dehydration (AAP/CDC)

Degree Weight loss Mild 3-5% normal Slightly dry normal Normal CRT normal normal normal normal Moderate 6-9% sunken dry *sunken orbits CRT > 2sec *normal to listless slightly normal Severe dehydration >10%

Skin turgor
Fontanelle Mucous mem. Eyes Extremities Neuro status Pulse volume Heart rate BP

normal (immed) *slow (<2 sec)

*v. slow (>2 sec)

sunken dry *deeply sunken cool, mottled *normal to lethargic or comatose mod. , (brady in v.sev.) normal to

UOP slightly Santosham M, 1ml/kg/hr management of acute diarrhea in < Glass RI. The << 1ml/kg/hr Sources: Adapted from Duggan C, children: oral rehydration, maintenance, and nutritional therapy. MMWR 1992;41(No. RR-16):120; Thirst slightly treatment of*mod. - eager *very thirsty andtoo and World Health Organization. The diarrhoea: a manual for physicians or other to drink lethargic senior health workers. Geneva, Switzerland: World Health Organization, 1995. to indicate

Assessment of Dehydration - WHO

Degree Weight loss No or minimal < 3% - 5% Some dehydration Severe dehydration moderate (6-10%) (>10%) +/- shock

Signs

< 2 of *

2 or more of *
*restlessness / irritability *sunken * - eager to drink not sunken > 2sec stable normal

2 or more of **
**abnormally sleepy or lethargic **v. slow (>2 sec) **sunken ** poorly or not at all sunken > 2sec circulatory collapse# tachypnoea, deep br.

Neuro status alert / active Skin pinch Eyes Thirst AF CRT CVS RR
#

normal (immed) *slow (<2 sec) not sunken normal normal <2 sec stable normal

Weak rapid pulse, cool or blue extremities, CRT, or hypotension

Skin pinch test showing laxity with dehydration *Pitfall: Skin pinch may not be elicitable in hypernatremic dehydr.

Child with severe dehydration Poor GC Drowsy Sunken eyes Chest risen due to deep breathing in response to acidosis

Case 1
8 month old baby 2 day h/o:
Mod. fever, intermittent Loose watery stools x10 /d, mucus +, no blood, mod. large amount Vomiting 3 times 1 day, no htemesis, food and fluids given, mod. amt UOP fair, passed with stools

O/E:
T 100F, irritable, feeding vigorously, eyes slightly sunken, no tears seen, tongue dry, skin pinch slightly lax (<2 sec), CRT =2 sec, pulse 140/min, p. pulses good vol, BP 85/ 50mmHg Abdomen soft, CVS, RS: NAD Weight 7.6 kg (5% from 8kg)

Case 1
Assessment
AGE, DD UTI, Sepsis, Some dehydration Risk of dehydration + Nutritional status
Wt for age: 50th cent.

Needs Observation & Rehydration

Investigations - Basic
Stool RE (if ?bacterial AGE, dysentery or protracted diarrhoea)
Pus cells Shigella, Salmonella spp, enteropathogenic E.coli, RBC Shigella, enteropathogenic and enteroinvasive E.coli, Campylobacter, some Salmonella spp. Amoeba E. hystolytica trophozoites with ingested rbc Giardia lamblia cysts or trophozoites Reducing substances (in protracted diarrhoea with watery stools and perianal excoriation) lactose intolerance

Urine RE (if ?UTI, esp. in infant < 1yr) WBC counts with DC + platelets (if systemic infection or DF suspected CRP Electrolytes Na, K, Cl
If severe dehydration, high risk of dehydration or vomiting

Further Investigations complications

Blood gases for acid base status Urea, creatinine. If severe dehydration + Stool culture
If bloody diarrhoea / dysentery, HUS, stool pus cells, diarrhoea in immunocompromised, persistent diarrhoea

Blood culture
If sepsis +ve clinically or Ix

Hb / PCV / counts / Blood picture

If HUS

If surgical cause suspected

Abdominal USG pyloric stenosis, intussusception X-rays intestinal obstruction

Proctosigmoidoscopy
If severe sympt. of colitis or cause of inflammatory symptoms obscure after lab Ix

Management
Rehydration + replace ongoing losses
ORT Iv fluids

Antiemetics Probiotics Nutritional management Zinc supplementation Antibiotics - role Antidiarrhoeals role

Physiology of Rehydration
Enterotoxins inhibit GTPase activity cAMP Cl- secretion Na+ and fluid loss Preserved reabsorption by Na+ -glucose co-transporter (SGLT1) Amino acid stimulated Na+ co-transporter

ORS
ORS components New Old* ORS ORS ORS compog/L g/L nents 2.6 3.5 Sodium Chloride New Old* ORS ORS mmol/L mmol/L 75 90 65 80

Sodium chloride

Glucose, anhydrous 13.5

Potassium chloride Trisodium citrate, dihydrate 1.5 2.9

20

Glucose

75
20 10

110
20 10

1.5 Potassium 2.9 Citrate

Total

20.5

27.9 Total

245

310

*clinical trials Less hyponatremia with Na+ ORS in cholera, but not others

ORS (contd.)
Other formulations
Rice-based ORS
Shown efficacy in cholera diarrhoea Provides more glucose for utilizing glucose coupled Na co-transport Provides amino acids for amino acid coupled NA cotransport Taste not palatable, difficult to administer

Home prepared ORT solution

Pinch of salt + 2 teaspoons sugar to 1 litre of boiled cooled water

Important to prepare ORS following instructions strictly

Case 2
2 yr old child 2 day h/o:
High gr. fever, continuous Loose watery stools x10 /d, mucus +, no blood, large amount Vomited 8 times 1 day, no htemesis, taken breastfeeds and fluids, but vomited all UOP uncertain, ? with stools, last noticed previous night (8hrs)

O/E:
T 101F, drowsy, refusing feeds, eyes sunken, no tears seen, tongue dry, skin pinch (<2 sec), CRT >2 sec, pulse 150/min, p. pulses vol, cool peripheries Abdomen soft, RS: NAD CNS: no neck stiff., pupils ER

Case 2
Wt: 10.8 kg
No recent weight check

Ix:
TLC 25,000 CRP 45mg/dl stool R/E: awaiting

Assessment
AGE with sepsis, Severe dehydration circ. Shock + Risk of further dehydration + complications ?Electrolyte abnorm, metab. Acidosis, glycemia Nutritional status - ?10th cent.

C. Resuscitation (Sev. dehyd >10%)

Urgent IVF bolus 100 mL/kg of RL or n. saline

Age Infant <12mths 1 5 yrs

30ml/kg 70ml/kg Total 100ml/kg Over 1 hr Over 5 hrs Over 6 hrs Over hr Over 2 hrs Over 3 hrs

Reassess every 15-30 min + ORS 5ml/kg/hr as soon as able to take orally

usually after 3-4 hrs

Assess after 6 hrs Still severe dehydration, haemodynamically unstable, no UOP back to C (Resuscitation) CVS stable, moderate dehydration Go to step B.

B. Replacement (Some dehyd 3-9%)

Age Weight ORS (ml) Min. amt < 4 mths < 6kg 200-400 4-12 mths 6 - <10kg 400-700 1-2 yrs 10 - <12kg 700-900 2-5 yrs 12-19kg 900-1400

If vomiting,
wait 10 min and restart Antiemetics if repeated vomiting ondansetron iv or oral
(not in WHO protocol but recent research may be useful)

Reassess hydration after 4 hrs

Include weight check Categorize as no, some or severe dehydration Treat as appropriate stage A, B or C

Case 2

A. Maintenance - Minimal dehydr. (<3%)

Replace ongoing stool loses with ORS
WHO
< 2 yrs 50-100ml for each loose stool > 2 yrs 100-200ml for each loose stool

Other protocols
1 mL ORS for each 1gram loose stool or, 10 mL/kg body weight of ORS for each watery or loose stool, and 2 mL/kg body weight for each episode of emesis.

Other fluids in between ORS

breastfeeds, coconut water, rice cunjee, soup, yogurt drinks Fruit juices, cola and sports drinks are inappropriate

Continue age appropriate feeding

IV Fluids
Indications in Replacement phase:
Mod dehydration and unable to retain oral fluids because of persistent vomiting LOC Ileus Inability to closely supervise or give ORT

Problems:
Fluid overload Electrolytes disturbances occurrence of seizures
AAP - Practice Parameter: The management of Acute gastroenteritis in young children. Pediatrics1996.97(3);424-435.

IV Fluids

Rehydration (algorhythm from BMJ)

BMJ review - Based on WHO

Repletion phase (Mod Dehyd. 6-9%) - AAP

IVF or ORT by NG or oral at 100 mL/kg over 4-6 hrs. Which iv fluid? RLD or DNS, in infants <1yr n/2+5%D ( DNS) Additional ORS to replace ongoing loss of stool*.
1 mL ORS for each 1gram loose stool or, 10 mL/kg body weight of ORS for each watery or loose stool, 2 mL/kg body weight for each episode of emesis.

Hourly reassess:
hydration status calculate continuing stool and emesis losses and add ongoing losses to replacement.

After 4 hrs reassess hydration. If mild dehydration (3-

5%) go to mild dehydration

Repletion phase (mild-mod 3-5%) - AAP

Repletion phase
ORS by mouth or NG (or IVF) at 50 mL/kg over 4 hours. Which iv fluid? RLD or DNS, in infants <1yr DNS Additional ORS to replace ongoing loss of stool*.
1 mL ORS for each 1gram loose stool or, 10 mL/kg body weight of ORS for each watery or loose stool, and 2 mL/kg body weight for each episode of emesis.

Reassess hydration and replacement of ongoing losses at least 2 hourly.

After 4 hrs reassess hydration

If no dehydration go to Step A Maintenance phase

Nutritional Management - Dos

Feed as early as possible Milk
Continue breastfeeding - freq Formula need not be diluted when reintroduced

Other fluids coconut water, rice cunjee, soup, yogurt drinks

Resume normal (solid) diet when appetite returns

Yogurt lactobacillus Rice / cereal - complex carbohydrates more glucose and amino acids fluid reabsorption and stool volume Banana, fruit K+, high energy, fibre stool bulk - solid Vegetables fibre Fish / lean meat (proteins) amino acids help fluid reabsorption Mix with 1-2 teaspoons of vegetable oil

Nutritional Management Donts

Avoid foods high in fat and sugars
Commercial fruit juices, cola and sports drinks are inappropriate - sugar content, Na

Dont add sugar or glucose to coconut water Fruit juices should be prepared without adding sugar as far as possible All these can worsen diarrhoea

Pharmacological measures
Antiemetics Probiotics Zinc Antibiotics limited role Antidiarrhoeals no role

Antiemetics
Ondansetron - useful in reducing vomiting over 8 hrs
vomiting, oral intake, need for iv fluids, hospital admission A/E: diarrhoeal episodes and representation after discharge.

Some other antiemetics suggested:1

Dopamine antagonists
domperidone metoclopramide - not recommended for use in neonates (in any form). A/E: may increase gut motility

Promethazine
(not recommended for children <2 years in any form) A/E: drowsiness and complicates assessment

When to give: during oral replacement / iv replacement

1. Marc Bevan, et al. Proposal for the inclusion of anti-emetic medications (for children) in the who model list of essential medicines. Report - Second Meeting of the Subcommittee of EC on the Selection and Use of Essential Medicines, Geneva, 29 September to 3 October 2008. Elliott EJ, et al. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev 2006;(3):CD005506. Evidence-Based Child Health 2006 (in press). Cited in Elizabeth Jane Elliott. Acute gastroenteritis in children. BMJ 2007;334;35-40.

2.

Probiotics
Found to duration of diarrhoea and daily frequency of stools1
Lactobacillus rhamnosus and a mix of L. delbrueckii var bulgaricus, Streptococcus thermophilus, L. acidophilus, and Bifidobacterium bifidum2 Saccharomyces boulardii not shown significant difference 2
1. Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2003;(4):CD003048.
2.Canani BC et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 2007;335;340;online

Zinc supplementation
WHO recommends:
> 6 months: 20 mg /day for infants < 6 months: 10 mg /day 1 of zinc suppl. for 1014 days

Reduce severity and duration of diarrhoea2 Prevents re-infection3

1.WHO/UNICEF Joint statement Clinical Management of Acute Diarrhoea 2.Bahl, R., et al., Effect of zinc supplementation on clinical course of acute diarrhoea Report of a Meeting, New Delhi, 7-8 May 2001. Journal of Health, Population and Nutrition, vol. 19, no. 4, December 2001, pp. 338-346. 3.Bhutta Z.A., Black, R.E., Brown K. H., et al., Prevention of diarrhoea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials, Zinc Investigators Collaborative Group, Journal of Paediatrics, vol. 135, no. 6, December 1999, pp. 689-697.

Role of antibiotics
Most AGE do not require nor benefit from AB
A/E: AB diarrhoea, prolonged Salmonella excretion

Indicated for
AGE complicated by septicaemia with some bacterial infections Protozoal infections Giardia, Amoebic desentery Evidence of other systemic or severe local bacterial infection, eg. UTI, pharyngitis, otitis media, septicaemia, meningitis
WHO 2005. Management of Common illnesses with Limited Resources (Paediatric) - WHO 2005 Elizabeth Jane Elliott. Acute gastroenteritis in children. BMJ 2007;334;35-40. M S Murphy. Guidelines for managing acute gastroenteritis based on a systematic review of published research. Arch. Dis. Child. 1998;79;279-284

Role of antibiotics - Indications

Organism Shigella Vibrio cholerae Campylobacter Indication All All Early AB ampi, cipro / oflox, ceftrioxone doxycyline, tetracycline erythromycin

Salmonella

cefotaxime, ceftrioxone, ampicillin, chloramphenicol, cotrim Clostridium difficile Mod-severe illness metronid, vanco
WHO 2005. Management of Common illnesses with Limited Resources (Paediatric) - WHO 2005

Inf<3mth, typhoid, bacteraemia, localized suppuration

Role of antibiotics - Indications

Organism E. coli enterotoxigenic E. coli enteropathogenic E. coli enteroinvasive Aeromonas Indication Severe prolonged illness Nursery epidemics, life threatening All AB cotrimoxazole cotrimoxazole cotrimoxazole

Dysentery, prolonged cotrimoxazole diarrhoea

Giardia lamblia
Entamoeba histolytica

If stool Giardia metronidazole cysts or trophozoites If stool amoebic metronidazole trophozoites in rbc

WHO 2005. Management of Common illnesses with Limited Resources (Paediatric) - WHO 2005

Role of antidiarrheals
Not recommended Can mask dehydration and ongoing losses Inadequate evidence on safety

Medicines under research

Racecadotril antisecretory agent
an enkephalinase inhibitor preserves the antisecretory activity of enkephalins does not slow intestinal transit or promote bacterial overgrowth Promising as an adjunctive in stool output in clinical trials

Current guidelines do not emphasize use

not required in most cases, may be used only as an adjunct as mainstay of treatment is rehydration

On discharge advice
Prescribe
ORS Zinc supplements Probiotics

How to prepare and give ORS Continue to feed

breastfeeds, fluids and dietary advice

Hygeine
handwashing, avoiding bottle feeds, boiled water for drinking

How to recognize danger signs of dehydration

WHO lethargy/ irritability, thirst, sunken eyes, skin pinch

When to follow-up

Follow-up after discharge

Bring child immediately if:
Sick Lethargic, LOC Unable to drink or breast-feed Poor drinking UOP Develops fever Blood in stool
May need hospital admission

Not improving for 5 days

Prevention

Prevention
Intervention area Hygiene Sanitation Water supply Reduction of diarrhoea frequency 37% 32% 25%

Water quality Multiple

WHO 2006. Ref:

31% 33%

Fewtrell L et al. Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and metaanalysis. The Lancet Infectious Diseases, 2005, 5(1):4252.

Summary
Mainstay of treatment is rehydration saves lives Antiemetics useful in reducing vomiting, but may diarrhoea Probiotics useful in diarrhoea duration and freq Nutrition early feeding improves outcome and reinfection Zinc supplementation - severity and duration of diarrhoea and re-infection Antibiotics
not required and does not benefit in most cases [1A] Indicated for Shigella dysentery and septicaemia complicating other bacterial AGE

Antidiarrhoeals should not be used

Literature
Pocket Book of Hospital Care for Children Guidelines for the Management of Common Illnesses with Limited Resources - WHO 2005 Review of Medical Physiology WF Ganong Nelsons Paediatrics Forfar & Arneils Textbook of Paediatrics 6th ed Elizabeth Jane Elliott. Acute gastroenteritis in children. BMJ 2007;334;35-40. M S Murphy. Guidelines for managing acute gastroenteritis based on a systematic review of published research. Arch. Dis. Child. 1998;79;279-284 Practice Parameter: The management of Acute gastroenteritis in young children. Pediatrics1996.97(3);424-435. Managing Acute Gastroenteritis Among Children - Oral Rehydration, Maintenance, and Nutritional Therapy. CDC MMWR. November 21, 2003 / Vol. 52 / No. RR-16 WHO/UNICEF Joint statement. Clinical Management of Acute Diarrhoea. May 2004 Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2003;(4):CD003048. Canani BC et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 2007;335;340;online Marc Bevan, Elizabeth Seil, Robin Bell and Jane Robertson. Proposal for the inclusion of anti-emetic medications (for children) in the WHO model list of essential medicines. Report - Second Meeting of the Subcommittee of the Expert Committee on the Selection and Use of Essential Medicines, Geneva, 29 September to 3 October 2008